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PubMed2002

Measles outbreak in a Periurban area of Chandigarh: need for improving vaccine coverage and strengthening surveillance.

OBJECTIVE: An outbreak of measles was investigated in the periurban areas of Chandigarh Union Territory, during the months of December 1998 to February 1999. Mainly the children below 15 years of age were affected. The children of migrant labourers belonging to the neighbouring states of Uttar Pradesh and Bihar constituted the majority of population in the area under study. They belonged to lower socio economic status with low immunization coverage. METHODS: A total of 2968 houses were surveyed for epidemiological investigations in the areas of colony No. 5, Ramdarbar, Palsora and Pandit colony of Kajheri, covering a population of 14,601 and 7.3% (216/2968) of families were affected in the outbreak. RESULTS: Two hundred and eighty three cases of measles were reported with an attack rate of 4.5% and male to female ratio of (M:F) 5.3%:3.6%. Among the measles cases, 48.8% had received measles vaccination. The outbreak was investigated by detecting measles specific IgG/IgM antibodies either in acute or convalescent serum samples or both. Due to inadequate surveillance system and containment measures, the outbreak was in full swing during the winter months. Measles related complications were reported in 31.1% cases (i.e. diarrhoea in 15.2% and Pneumonia is 7.1%). CONCLUSION: Following smallpox and guinea worm eradication, WHO's next thrust, is on eradication of poliomyelitis and measles. Hence, strengthening of disease surveillance as well as vaccination policies are mandatory to achieve disease control in these areas.

Adolescent↗
PubMedDate not supplied

Enhancement in seroconversion to measles vaccine with simultaneous administration of vitamin A in 9-months-old Indian infants.

The mutual interactions of measles vaccine and vitamin A dose when administered simultaneously to 9 month old infants are explored in this study. One hundred healthy infants of 9 months of age received EZ strain of measles vaccine in the routine immunization clinic along with either 100,000 IU of vitamin A or a placebo orally. Blood samples were collected before and 4 weeks after intervention. They were coded and analysed for serum retinol and Hemagglutination Inhibition (HI) antibodies to measles. Ninety five per cent of the infants were seronegative to measles prior to vaccination with a seroconversion rate of 63% in the control group and a significantly higher percent of 83.7% in the experimental group (P < 0.01). Seroconversion was not related to initial serum retinol levels in either of the groups. 42% of infants had serum retinol levels less than 20 ug/dl before administration of the vaccine and both the groups showed improvement in vitamin A status following intervention, the increase being significant in the experimental group (from 22.4 +/- 1.32 to 26.0 +/- 1.07; P < 0.05). The results indicate that majority of the infants at 9 months of age were seronegative to measles. Seroconversion to measles vaccine in the routine immunization clinics was low. Simultaneous administration of vitamin A and measles vaccine had beneficial effects on vitamin A status as well as seroconversion rates to the vaccine in 9 months old infants.

Analysis of Variance↗
PubMed1982

A study of measles virus and canine distemper virus antibodies, and of childhood infections in multiple sclerosis patients and controls.

We investigated the levels of neutralizing antibodies to measles virus and canine distemper virus (CDV) in 72 multiple sclerosis patients (MS) and matched controls and also examined the frequency and age of onset of a number of childhood illnesses, including measles. The frequency of each childhood illness was not significantly different between cases and controls, but cases did report a later age at measles infection. Our data suggest that the risk of MS is increased by a factor of 1.9 if measles infection occurs between 5 and 9 years of age. A validity survey, based on a questionnaire to general practitioners, suggested substantial inaccuracy in the patients' reports of when they had measles, but the direction and degree of inaccuracy did not appear to be different between cases and controls. We also found higher titres of neutralizing antibodies in cases than controls to both measles virus and CDV, although the CDV difference was not statistically significant. In the light of a significant correlation between measles and CDV titres in both cases and controls, we used paired logistic regression to determine if the case-control difference in titres for each virus could be explained by a confounding effect on one by the other. The numbers were too small, however, to enable us to separate out any independent association of either virus with MS.

Age Factors↗
PubMed1979

Immunization against measles in children at risk for severe disease.

Live measles vaccine induced protective levels of antibody in 70% of children with protein-calorie-malnutrition (PCM) within 21 days and possibly in 90% by 42 days. The development of specific antibody was delayed and symptoms due to the vaccine more frequent (64%) in these children than in healthy children. Administration of measles vaccine may have predisposed to an associated fatal pneumonia in one malnourished child. Human measles hyperimmune globulin can maintain adequate antibody levels in most children with PCM (75%) for at least three to four weeks. Vaccination induced protective levels of measles antibody in 83% of healthy children under 10 months of age, which compared well with 86% of successful immunizations done at 10 months or later. There was wastage of vaccine in 40 to 70% of children who, despite a negative history of measles, had protective levels of antibody when admitted to the study. It is suggested that malnourished children in the community or the very young can be safely and effectively vaccinated against measles. But passive immunization is preferred in children with PCM severe enough to be admitted to hospital and thereby at increased risk of exposure to measles and other infections.

Antibodies, Viral↗
PubMedDate not supplied

Detection of IgM antibodies specific for measles virus by capture and indirect enzyme immunoassays.

During a measles outbreak, 112 serum specimens from 88 hospitalized patients were received in our laboratory for investigation of a morbilliform rash. These specimens (88 acute- and 24 convalescent-phase) were tested for the presence of measles-specific IgM antibodies by a capture EIA (enzyme immunoassay) using peroxidase-conjugated measles virus antigens and by an indirect EIA. Commercially available indirect EIA kits for measles-specific IgM antibodies were also used and compared with our homemade EIAs. Specificity studies included a collection of serum specimens containing rheumatoid factor, antinuclear antibodies or IgM antibodies specific to other viruses, and sera from blood donors and healthy children. Sensitivity of capture EIA and indirect EIA to detect measles IgM was 91.8 and 90.3%, respectively, and specificity was 98.2% for both tests. Specific IgM antibodies were detected in 70.5% of serum specimens at the first day after rash onset and were present for a month following the rash. Among the commercial measles IgM detection assays, EIA "Behring" was found to be a valid alternative for detection of measles virus-specific IgM.

Adolescent↗
PubMed2005

Extinction of the human leukocyte antigen homozygosity effect after two doses of the measles-mumps-rubella vaccine.

We have reported associations between human leukocyte antigen (HLA) homozygosity and low measles antibody levels after one dose of the measles, mumps, and rubella (MMR) vaccine. Here, we examined associations between HLA homozygosity and immune responses to MMR after two doses of vaccine. We examined associations between HLA homozygosity and measles antibody levels in a group of 178 children (cohort 1) as well as associations between homozygosity and antibody levels and lymphoproliferative responses to MMR in 346 children (cohort 2). In cohort 1, HLA homozygotes and heterozygotes had similar increases in measles antibody levels after a second dose of measles vaccine. In cohort 2, HLA homozygosity was not associated with measles immune measures after two doses of vaccine. Homozygosity at the DPB locus was associated with increased rubella antibody levels, and homozygosity at the class IA alleles was associated with lower mumps lymphoproliferative response. Homozygosity at increasing numbers of loci was also associated with lower mumps antibody levels and lymphoproliferative response. Therefore, two doses of the MMR vaccine appear to induce sufficient antibody levels and lymphoproliferative responses against measles and rubella, regardless of HLA homozygosity status. However, children who are HLA homozygous may be less protected against mumps compared with children who are heterozygous.

Antibodies↗
PubMed2004

Acute infectious mononucleosis and coincidental measles virus infection.

BACKGROUND: Both Epstein-Barr and measles viruses (MV) cause immune suppression, and the association of the two viruses is evaluated as life threatening. The cell immune impairment caused by simultaneous Epstein-Barr and measles viral infections was responsible for the complicated course of the disease in all described previously reports and for unfavorable outcomes in most of the cases. Timely diagnosis of coincidental viral infections could be a useful predictor for the clinical course and complications. Diagnosis must be based on an accurate assessment of clinical, hematologic, serologic manifestations and supported by appropriate laboratory methods. Recognizing the infectious etiology of concomitant infections is important for both clinicians and epidemiologists. OBJECTIVE: To describe a case report of a 20-year-old woman previously vaccinated against measles infected with acute mononucleosis and coincidental measles virus infection. STUDY DESIGN: The clinical, routine laboratory, as well as serological and virologic findings of this patient were scrutinized. Special emphasis was placed on the use of RT-PCR/PCR for confirming the involvement of both measles virus and Epstein-Barr virus (EBV) in this patient's illness. RESULTS: Infectious mononucleosis was not suspected at admission to the hospital. The final diagnosis of a concomitant measles virus infection and acute infectious mononucleosis was facilitated using viral serology to detect virus-specific IgG and IgM antibodies and by RT-PCR for the detection of measles virus RNA and EBV DNA from peripheral blood monocyte cells (PBMC). CONCLUSION: The present report highlights the difficulty of diagnosing two coincidental virus infections on clinical grounds. Serological and molecular laboratory methods, specifically the PCR (RT-PCR) analysis, are found to be useful for confirming the concomitant viral infections and proper identification of the infecting pathogens.

Acute Disease↗
PubMed2006

Suppression of NF-kappaB and AP-1 activation in monocytic cells persistently infected with measles virus.

A major cause of the high morbidity and mortality associated with measles infection is attributed to virus-mediated immunosuppression. In this report, we present evidence for a novel strategy of immunosuppression by the measles virus. We observed a marked suppression of lipopolysaccharide (LPS)-induced IL-8, RANTES, TNF-alpha and IL-6 production and NF-kappaB activation in human monocytic cell lines persistently infected with measles virus. This effect was not observed in human epithelial cells lines persistently infected with measles virus. There were no significant differences in expression levels of Toll-like receptors (TLRs) and their associated molecules, or other intracellular signaling molecules of the NF-kappaB signaling pathway in measles-virus-infected monocytic cells compared to uninfected cells. Infected monocytic cells exhibited decreased LPS-induced DNA binding of NF-kappaB and phosphorylation of JNK, namely activation of transcription factors NF-kappaB and AP-1. NF-kappaB was constitutively activated in human epithelial cells persistently infected with measles virus, and LPS treatment resulted in further activation. The cell-type-specific suppression of NF-kappaB activation represents a potential strategy of escape from the host immune system by measles virus via induced immunological silencing in infected cells.

Cell Line↗
PubMedDate not supplied

A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal.

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

Cohort Studies↗
PubMed2003

Naturally processed measles virus peptide eluted from class II HLA-DRB1*03 recognized by T lymphocytes from human blood.

This is the first report of the direct identification of a HLA-DRB1*03 measles-derived peptide from measles virus infected EBV-transformed B cells. We purified HLA-DR3-peptide complexes from EBV-B cells infected with measles virus (Edmonston strain) and sequenced the HLA-DR3-peptides by mass spectrometry. A class II peptide, derived from a measles phosphoprotein, ASDVETAEGGEIHELLRLQ (P1, residues 179-197), exhibited the capacity to stimulate peripheral blood mononuclear cells to proliferate. Our data provides direct evidence that the antigenic peptide of measles virus was processed by antigen-presenting cells, presented in the context of HLA class II molecules, and was recognized by peripheral blood T cells from healthy individuals previously immunized with measles vaccine. The approach described herein provides a useful methodology for the future identification of HLA-presented pathogen-derived epitopes using mass spectrometry. The study of cell-mediated immune responses to the measles-derived peptide in immune persons should provide significant insight into the design and development of new vaccines.

Adolescent↗
PubMed1992

Measles: lessons from an outbreak.

BACKGROUND: Measles outbreaks continue to be a problem for infection control in hospitals--patients, personnel, and employee health service. Guidelines for measles outbreaks are not clear for medical personnel in the hospital. METHODS: Outbreak investigation in a university-affiliated teaching hospital. RESULTS: Four primary cases resulted in 607 staff exposures and two secondary cases. Forty-seven medical personnel were furloughed and 88 were vaccinated for measles. Minimal serologic criteria for immunity were found to be inadequate in the outbreak setting. CONCLUSIONS: We found that serologic guidelines for assessing immunity to measles are inadequate. During the outbreak, we arbitrarily doubled the acceptable enzyme-linked immunosorbent assay titers that we would consider protective, > or = 2, to decrease the possibility of further secondary cases. Employees with enzyme-linked immunosorbent assay measles titers less than 2 and without a definite history of natural measles were revaccinated with a measles vaccine. This strategy takes advantage of the anamnestic response that revaccination would confer in persons with low antibody titer.

Adult↗
PubMed2001

Induction of cytokine mRNA in peripheral blood mononuclear cells of infants after the first dose of measles vaccine.

To better characterize the cytokine response to measles virus vaccine, we examined the levels of IL-2, IL-4, IL-5, IL-10, IL-12 and gamma-interferon (gamma-IFN) in measles virus-stimulated peripheral blood mononuclear cells from 18 donors before and 2 weeks after vaccination. Donors were grouped as seropositive or seronegative on the basis of measles-specific IgM antibody present at 2 weeks postvaccination. After vaccination, similar levels of upregulation of IL-2 and gamma-IFN mRNA were observed in the two groups. The majority of donors in both groups did not exhibit an increase in measles specific IL-4 or IL-10 mRNA after vaccination. IL-12 mRNA was not induced by measles virus in any of the donors. A statistically significant upregulation of IL-5 mRNA was observed among seropositive (9/13) compared with seronegative (1/5) donors after vaccination (P=0.09, one tailed Fisher's test). The observed measles specific induction of IL-5 mRNA is suggestive of a possible association between IL-5 production and an antibody response to measles virus.

Antibodies, Viral↗
PubMedDate not supplied

Safety and characterization of the immune response engendered by two combined measles, mumps and rubella vaccines.

We performed a randomized trial to compare the safety and immunogenicity of two combined measles, mumps and rubella vaccines in healthy children 14-24 months of age. Triviraten Berna Vaccine (Swiss Serum and Vaccine Institute), contains the Edmonston Zagreb 19 strain of measles virus, the Rubini mumps virus strain and the Wistar RA 27/3 rubella strain while MMR-Vax (Merck, Sharp & Dohme, West Point, PA) contains the Enders attenuated Edmonston measles strain, the Jeryl Lynn mumps strain and the Wistar RA 27/3 rubella strain. Immunization with Triviraten Berna was associated with a significantly lower incidence of swelling and redness at the injection site in addition to a reduced rate of fever compared with MMR-Vax. Seroconversion rates for the measles and rubella vaccine components were comparable in all tests used. However, seroconversion for the mumps vaccine component was test-dependent. Using an ELISA, the seroconversion rate following immunization with MMR-Vax was significantly (P < 0.01) higher than for Triviraten Berna. In contrast, nearly identical rates were obtained using an indirect immunofluorescence test. Both vaccines were equally effective at engendering antibodies capable of neutralizing wild type mumps virus. Geometric mean ELISA antibody titers against measles and mumps virus were higher following immunization with MMR-Vax while that for rubella was higher after immunization with Triviraten Berna. A small number (N = 13) of adolescents immunized either with MMR-Vax or Triviraten Berna were reimmunized with Triviraten Berna and various humoral and cellular response parameters to the measles and mumps vaccine components analyzed. While few subjects mounted a humoral antibody response to measles, most likely due to elevated baseline titers, there was a marked lymphoproliferative response. Anti-mumps virus ELISA antibody titers were higher both at baseline and after reimmunization in subjects who received MMR-Vax for primary immunization. However, there was no difference in either neutralizing titer or proliferative response in subjects primed with MMR-Vax or Triviraten Berna either before or after reimmunization.

Antibodies, Viral↗
PubMed2003

Lack of association between transporter associated with antigen processing (TAP) and HLA-DM gene polymorphisms and antibody levels following measles vaccination.

The transporter associated with antigen processing (TAP) and human leukocyte antigen-DM (HLA-DM) genes are involved in the antigen-processing pathway of both HLA class I and class II-restricted antigen presentation. We hypothesized that polymorphisms within the TAP and DM genes may influence antibody levels following measles vaccination. We examined TAP and DM polymorphisms in 242 school children from Olmsted County, Minnesota, USA who received one dose of measles-mumps-rubella-II (MMR-II) vaccine at the age of 15 months. Based on the level of serum measles-specific immunoglobulin G (IgG) antibodies, subjects were classified as seronegatives (n = 72) or seropositives (n = 170). We determined TAP1 and TAP2 allele types by polymerase chain reaction (PCR) amplification of specific alleles (PASA) and determined DM allele type by PCR amplification followed by direct sequencing of the polymorphic sites. We analysed the data for any TAP or DM allelic association with antibody levels post measles vaccination using the chi-square test and univariate linear regression analysis. We found no trend in the overall distribution of TAP and DM genotype frequencies between seronegative and seropositive subjects, suggesting that TAP and DM polymorphism and antibody levels following measles vaccination are not directly associated. In addition, we did not find an association between TAP (TAP1, P = 0.71; TAP2, P = 0.87) or DM (DMA, P = 0.42; DMB, P = 0.71) homozygosity and seronegativity to measles vaccine in this study group. Our study suggests that TAP and DM gene polymorphisms do not influence antibody levels post measles vaccination.

ATP-Binding Cassette Transporters↗
PubMed1989

Immune activation in measles.

Measles is associated with alterations in immune regulation that sometimes lead to secondary infections or autoimmune encephalomyelitis. Simultaneously, an effective measles virus-specific immune response develops. To relate immune activation to measles and its complications, we studied the spontaneous proliferation of blood mononuclear cells and circulating levels of soluble interleukin-2 receptor and CD8 T-cell antigens in 126 patients with complicated or uncomplicated measles at various stages of the disease. Spontaneous proliferation of mononuclear cells, which was present through the first week of the rash, was greater in cells from patients with measles (8787 +/- 1403 cpm) than in those from healthy children (1529 +/- 237 cpm, P less than 0.0001). Levels of soluble interleukin-2 receptor (3385 +/- 195 units per milliliter) and CD8 (4145 +/- 437 units per milliliter) were higher in patients with measles than in those with other infectious diseases (2377 +/- 440, P = 0.003; 2399 +/- 771, P = 0.0374) or in healthy children (865 +/- 138, P less than 0.0001; 1026 +/- 169, P less than 0.0001). Levels of soluble interleukin-2 receptor were elevated before the onset of the rash and remained elevated for several weeks. In contrast, levels of soluble CD8 increased only when the rash appeared, and subsided quickly. Spontaneous proliferation of mononuclear cells and levels of soluble CD8 were similar in patients with uncomplicated disease, pneumonia, or encephalomyelitis, but soluble interleukin-2 receptor levels were lower in patients with encephalomyelitis (2312 +/- 314 vs. 3455 +/- 247 units per milliliter in uncomplicated measles; P = 0.01). In patients with encephalomyelitis, cerebrospinal fluid levels of soluble CD8 (686 +/- 350 units per milliliter), but not interleukin-2 receptor (9 +/- 8.3 units per milliliter), were increased. We conclude that the proliferative phase of the immune response, as measured by the release of soluble interleukin-2 receptor, begins before the rash appears, continues for several weeks in those without complications, but does not occur within the nervous system. In contrast, the effector phase of the immune response, as measured by the release of soluble CD8, coincides with the appearance and disappearance of the rash and occurs within the nervous system during encephalomyelitis.

Adolescent↗
PubMed1985

Measles in young adults. The case for vigorous pursuit of immunization.

Although the incidence of measles has reached record low levels in the United States, measles continues to occur in young adults. No single public health measure can ensure immunity for young adults, as school immunization laws do for young children. Therefore, to eliminate measles in this age-group, clinicians must take the initiative to vaccinate or revaccinate patients. To facilitate containment of outbreaks of measles, clinicians should include measles in the differential diagnosis of any illness characterized by fever and a generalized rash and should promptly report these cases as suspected measles to local health departments, without waiting for laboratory confirmation. If the suspected case is indeed measles, a significant outbreak could be avoided long before the first laboratory results are known.

Adolescent↗
PubMed1975

Immunologic injury in measles virus infection. II. Suppression of immune injury through antigenic modulation.

Upon the addition of antibody to measles virus, measles virus antigens expressed on the surface of infected cells can be modulated from the cell's membrane in vitro. Removal of measles virus antigens from the surface of cells occurs relatively rapidly and is accompanied by a parallel reduction in the ability of antibody and complement to lyse these cells. Modulation of surface viral antigens can occur in the absence of cap formation and is fully reversible once measles virus antibodies are removed from culture medium. Protracted exposure of acutely infected cells to measles virus antibodies results in a population of cells that exhibit normal cytomorphology and growth behavior. These cells continue to express measles virus antigens internally, but not at the cell surface, and are refractory to immune lysis. Once antiviral antibody is removed, measles virus antigens again appear on the cell surface, giant cell and syncytial formation occur, and cell death follows. These observations may explain the persistence of virus in spite of a vigorous host antiviral immune response in certain chronic infections of man.

Antibodies, Viral↗
PubMed2003

Measles incidence before and after mass vaccination campaigns in Burkina Faso.

Burkina Faso conducted mass measles vaccination campaigns among children aged 9 months to 4 years during December 1998 and December 1999. The 1998 campaign was limited to six cities and towns, while the 1999 campaign was nationwide. The last year of explosive measles activity in Burkina Faso was 1996. Measles surveillance data suggest that the 1998 urban campaigns did not significantly impact measles incidence. After the 1999 national campaign, the total case count decreased during 2000 and 2001. However, 68% of measles cases occurred among children aged 5 years or older who were not included in the mass vaccination strategy. During 2000 and 2001, areas with high measles incidence were characterized by low population density and presence of mobile and poor populations. Measles control strategies in Sahelian Africa must balance incomplete impact on virus circulation with cost of more aggressive strategies that include older age groups.

Burkina Faso↗